Document Detail


PPARgamma controls dectin-1 expression required for host antifungal defense against Candida albicans.
MedLine Citation:
PMID:  20062524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We recently showed that IL-13 or peroxisome proliferator activated receptor gamma (PPARgamma) ligands attenuate Candida albicans colonization of the gastrointestinal tract. Here, using a macrophage-specific Dectin-1 deficient mice model, we demonstrate that Dectin-1 is essential to control fungal gastrointestinal infection by PPARgamma ligands. We also show that the phagocytosis of yeast and the release of reactive oxygen intermediates in response to Candida albicans challenge are impaired in macrophages from Dectin-1 deficient mice treated with PPARgamma ligands or IL-13. Although the Mannose Receptor is not sufficient to trigger antifungal functions during the alternative activation of macrophages, our data establish the involvement of the Mannose Receptor in the initial recognition of non-opsonized Candida albicans by macrophages. We also demonstrate for the first time that the modulation of Dectin-1 expression by IL-13 involves the PPARgamma signaling pathway. These findings are consistent with a crucial role for PPARgamma in the alternative activation of macrophages by Th2 cytokines. Altogether these data suggest that PPARgamma ligands may be of therapeutic value in esophageal and gastrointestinal candidiasis in patients severely immunocompromised or with metabolic diseases in whom the prevalence of candidiasis is considerable.
Authors:
Amandine Galès; Annabelle Conduché; José Bernad; Lise Lefevre; David Olagnier; Maryse Béraud; Guillaume Martin-Blondel; Marie-Denise Linas; Johan Auwerx; Agnès Coste; Bernard Pipy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-08
Journal Detail:
Title:  PLoS pathogens     Volume:  6     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-11     Completed Date:  2010-03-09     Revised Date:  2010-09-28    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1000714     Citation Subset:  IM    
Affiliation:
UMR-MD3 EA2405 Université de Toulouse III; UPS; Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, PMRNP2I, Toulouse, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Candida albicans / immunology
Candidiasis / immunology*,  metabolism
Cell Separation
Flow Cytometry
Interleukin-13 / immunology,  metabolism
Lectins, C-Type / immunology,  metabolism
Macrophage Activation / immunology
Macrophages / immunology,  metabolism*
Mannose-Binding Lectins / immunology,  metabolism
Membrane Proteins / immunology,  metabolism*
Mice
Mice, Knockout
Nerve Tissue Proteins / immunology,  metabolism*
PPAR gamma / immunology,  metabolism*
Phagocytosis / immunology
Reactive Oxygen Species / immunology,  metabolism
Receptors, Cell Surface / immunology,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / immunology*
Chemical
Reg. No./Substance:
0/Interleukin-13; 0/Lectins, C-Type; 0/Mannose-Binding Lectins; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/PPAR gamma; 0/Reactive Oxygen Species; 0/Receptors, Cell Surface; 0/dectin 1; 0/mannose receptor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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